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Iris Navarro-Millán, Erika Darrah, Andrew O Westfall, Ted R Mikuls, Richard J Reynolds, Maria I Danila, Jeffrey R Curtis, Antony Rosen, S Louis Bridges
BACKGROUND: Evidence suggests that the presence of peptidyl arginine deiminase type 4 (PAD4) antibodies is associated with radiographic-severity rheumatoid arthritis (RA) among Caucasian patients. The presence of anti-PAD4 antibodies that were cross-reactivity against PAD3 was associated with more aggressive erosive disease (compared with the presence of anti-PAD4 antibodies without anti-PAD3 crossreactivity) in Caucasian RA patients. The objectives of this study were to determine the prevalence of serum anti-PAD4 and anti-PAD4/PAD3 cross-reactive autoantibodies in African Americans with RA and whether these antibodies associate with radiographic severity and radiographic progression...
October 22, 2016: Arthritis Research & Therapy
Sanna Turunen, Johanna Huhtakangas, Tomi Nousiainen, Maarit Valkealahti, Jukka Melkko, Juha Risteli, Petri Lehenkari
BACKGROUND: Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase. METHOD: Total of 195 synovial samples from metatarsal joints from five ACPA/RF-positive RA patients (n = 77), synovial samples from knees of eight seropositive RA (n = 60), seven seronegative RA (n = 33) and five osteoarthritis (n = 25) patients were analyzed for citrulline and homocitrulline contents using HPLC...
October 20, 2016: Arthritis Research & Therapy
Bryant R England, Geoffrey M Thiele, Ted R Mikuls
PURPOSE OF REVIEW: This article reviews recent literature on the origin and pathogenic role of anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA). RECENT FINDINGS: ACPAs and ACPA-immune complexes interact with immune cells to facilitate articular inflammation. Findings from recent in vitro and in vivo studies are congruent with epidemiologic observations in RA supporting a pathogenic role of ACPAs. SUMMARY: ACPAs target proteins/peptides with citrullinated epitopes and serve as informative RA biomarkers...
October 13, 2016: Current Opinion in Rheumatology
C M Mariaselvam, C Fortier, D Charron, R Krishnamoorthy, R Tamouza, V S Negi
Rheumatoid arthritis (RA) is a complex multifactorial autoimmune disease characterized by inflammatory arthritis. The precise etiology and pathogenesis of RA remains elusive but evidence points towards stochastic interactions between genetic and environmental factors. This study investigated the distribution of human leucocyte antigen (HLA)-DRB1/DQB1 alleles in South Indian patients with rheumatoid arthritis (RA) and their influence on RA susceptibility and clinical phenotype. Low resolution HLA-DRB1 and -DQB1 typing was performed in 271 RA patients and 233 healthy controls by polymerase chain reaction (PCR) using sequence-specific primers (SSP)...
November 2016: HLA
Eric Hatterer, Limin Shang, Pierre Simonet, Suzanne Herren, Bruno Daubeuf, Stéphanie Teixeira, James Reilly, Greg Elson, Robert Nelson, Cem Gabay, Jeremy Sokolove, Iain B McInnes, Marie Kosco-Vilbois, Walter Ferlin, Emmanuel Monnet, Cristina De Min
BACKGROUND: Increased expression of toll-like receptor 4 (TLR4) and its endogenous ligands, is characteristic of rheumatoid arthritis (RA) synovitis. In this study, we evaluated how these TLR4 ligands may drive pathogenic processes and whether the fine profiling of anti-citrullinated protein antibodies (ACPA) based on their target specificity might provide a simple means to predict therapeutic benefit when neutralizing TLR4 in this disease. METHODS: The capacity of RA synovial fluids (RASF) to stimulate cytokine production in monocytes from patients with RA was analyzed by ELISA...
October 6, 2016: Arthritis Research & Therapy
Serena Bugatti, Laura Bogliolo, Barbara Vitolo, Antonio Manzo, Carlomaurizio Montecucco, Roberto Caporali
BACKGROUND: Autoantibodies such as anti-citrullinated protein antibodies (ACPA) are major risk factors for articular bone destruction from the earliest phases of rheumatoid arthritis (RA). The aim of the current study was to determine whether RA-associated autoantibodies also impact on systemic bone loss in patients with early disease. METHODS: Systemic bone mineral density (BMD) was measured in the lumbar spine and the hip in 155 consecutive treatment-naïve patients with early RA (median symptom duration 13 weeks)...
October 6, 2016: Arthritis Research & Therapy
Laura Geraldino-Pardilla, Jon T Giles, Jeremy Sokolove, Afshin Zartoshti, William H Robinson, Matthew Budoff, Robert Detrano, Sabahat Bokhari, Joan M Bathon
OBJECTIVE: Citrullinated proteins have been found within atherosclerotic plaque. However, to date studies evaluating the association between anti-citrullinated peptide antibodies (ACPAs) and imaging measures of atherosclerosis in patients with rheumatoid arthritis (RA) have been limited to citrullinated-fibrinogen or citrullinated-vimentin seroreactivities and rendered contradictory results. Therefore, our objective was to evaluate this association using an extended panel of ACPAs in a larger sample of RA patients without clinical cardiovascular disease (CVD)...
October 1, 2016: Arthritis Care & Research
Mohammad Nasehi, Elnaz Rostam-Nezhad, Mohaddeseh Ebrahimi-Ghiri, Mohammad-Reza Zarrindast
Functional interaction between cannabinoid and serotonin neuronal systems have been reported in different tasks related to memory assessment. The present study investigated the effect of serotonin 5-HT4 agents into the dorsal hippocampus (the CA1 region) on spatial and object novelty detection deficits induced by activation of cannabinoid CB1 receptors (CB1Rs) using arachidonylcyclopropylamide (ACPA) in a non-associative behavioral task designed to forecast the ability of rodents to encode spatial and non-spatial relationships between distinct stimuli...
September 26, 2016: Behavioural Brain Research
Paola Conigliaro, Paola Triggianese, Maria Sole Chimenti, Ramona Lucchetti, Barbara Kroegler, Roberto Perricone
OBJECTIVE: To evaluate prospectively serological markers at baseline and during treatment in patients with rheumatoid arthritis (RA) initiating rituximab treatment, following failure of antitumour necrosis factor (TNF)-α therapy. METHODS: Patients with RA and healthy control subjects were recruited. Plasma complement (C)3, C4, rheumatoid factor (RF), anticitrullinated protein antibody (ACPA), immunoglobulin (Ig)M, A and G, disease activity scores (DAS) and therapeutic response were recorded at baseline and at 6, 12 and 18 months...
September 2016: Journal of International Medical Research
Stefano Alivernini, Mariola Kurowska-Stolarska, Barbara Tolusso, Roberta Benvenuto, Aziza Elmesmari, Silvia Canestri, Luca Petricca, Antonella Mangoni, Anna Laura Fedele, Clara Di Mario, Maria Rita Gigante, Elisa Gremese, Iain B McInnes, Gianfranco Ferraccioli
MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD(-)CD27(-) memory B-cell population in ACPA(+) RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU...
September 27, 2016: Nature Communications
Y El Miedany, M El Gaafary, S Youssef, I Ahmed, Sami Bahlas, M Hegazi, A Nasr
This study aims to assess clinical, lab/immunological or imaging (joint ultrasonography) markers able to predict disease relapse in RA patients in sustained remission when tapering or stopping their treatment. One hundred fifty-seven RA patients in clinical remission (DAS-28 <2.6 for >6 months), receiving treatment with sDMARDs and bDMARD therapy, were randomly allocated into any of five groups: Group 1: continue full dose DMARDs and taper biologic therapy by 50 % (31 patients); Group 2: taper both DMARDs and biologic therapy dose by 50 % (32 patients); Group 3: taper DMARDs by 50 % and stop biologic therapy (31 patients); Group 4: stop both DMARDs and biologic therapy (31 patients); Group 5: continue medications without change (31 patients)...
September 22, 2016: Clinical Rheumatology
Adeline Ruyssen-Witrand, Yannick Degboé, A Cantagrel, D Nigon, C Lukas, S Scaramuzzino, Y Allanore, O Vittecoq, T Schaeverbeke, J Morel, J Sibilia, A Cambon-Thomsen, P Dieudé, A Constantin
OBJECTIVES: The RANK/RANKL/osteoprotegerin (OPG) system plays a central role in the pathogenesis of bone erosions in rheumatoid arthritis (RA). The aim of this study was to test the association between 11 single-nucleotide polymorphisms (SNPs) located on RANK, RANKL and OPG genes and anticitrullinated peptide antibody (ACPA) presence or erosions in RA. METHODS: HASH(0x4a72560) PATIENTS: This work was performed on three independent samples of French patients with RA: the Etude de Suivi des PolyArthrites Indifférenciées Récentes (ESPOIR) (n=632), Rangueil Midi-Pyrénées (RMP) (n=249) and French Rheumatoid Arthritis Genetic Consortium (FRAGC) (n=590) cohorts...
2016: RMD Open
Lesley-Anne Bissell, Elizabeth M A Hensor, Lukasz Kozera, Sarah L Mackie, Agata N Burska, Jacqueline L Nam, Helen Keen, Edith Villeneuve, Helena Donica, Maya H Buch, Philip G Conaghan, Jacqueline Andrews, Paul Emery, Ann W Morgan
OBJECTIVES: To determine the change in established biomarkers of cardiovascular (CV) risk, namely, total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C), N-terminal pro-brain natriuretic peptide (NT-proBNP) and insulin resistance (IR) in patients with early RA treated with two different treat-to-target strategies. METHODS: Fasting glucose, lipids, insulin and NT-proBNP were measured at baseline, weeks 26 and 78 in 79 DMARD-naïve RA patients, free of CV disease, as part of a double-blind randomized controlled trial of MTX with either infliximab (IFX) or methylprednisolone as induction therapy...
September 16, 2016: Rheumatology
Bruno Fautrel, Jacques Morel, Jean-Marie Berthelot, Arnaud Constantin, Michel De Bandt, Philippe Gaudin, Jean-Francis Maillefert, Olivier Meyer, Thao Pham, Alain Saraux, Elisabeth Solau-Gervais, Olivier Vittecoq, Daniel Wendling, Marie-Line Erpelding, Francis Guillemin
: Fluctuating disease activity may affect rheumatoid arthritis (RA) progression. Previously, we developed a self-administered questionnaire to detect RA flares in the 3 months since the last visit to the rheumatologist. OBJECTIVES: To validate the measurement properties and the detection performance of the FLARE-RA questionnaire in a longitudinal prospective study. METHODS: A prospective trial of RA patients documented: 1) content and construct validity by factor analysis (FA), convergent validity by Pearson correlation with routine assessment of patient index data (RAPID3), RA impact of disease (RAID) score, DAS28 and HAQ; 2) reliability (intraclass correlation coefficient [ICC] and Bland and Altman plot); 3) feasibility of use...
September 16, 2016: Arthritis & Rheumatology
Tue Bjerg Bennike, Torkell Ellingsen, Henning Glerup, Ole Kristian Bonderup, Thomas Gelsing Carlsen, Michael Kruse Kruse Meyer, Martin Bøgsted, Gunna Christiansen, Svend Birkelund, Vibeke Andersen, Allan Stensballe
Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. To gain new insight into the systemic immune manifestations of RA, we characterized the colon mucosa proteome from 11 RA-patients and 10 healthy controls. The biopsies were extracted by colonoscopy and analyzed by label-free quantitative proteomics, enabling the quantitation of 5,366 proteins. The abundance of dihydrofolate reductase (DHFR) was statistically significantly increased in RA-patient biopsies compared to controls, and correlated with the administered dosage of methotrexate (MTX), the most frequently prescribed immunosuppressive drug for RA...
September 14, 2016: Journal of Proteome Research
Gisele Zandman-Goddard, Alessandra Soriano, Boris Gilburd, Merav Lidar, Shaye Kivity, Ron Kopilov, Pnina Langevitz, Yehuda Shoenfeld, Nancy Agmon-Levin
No abstract text is available yet for this article.
September 13, 2016: Immunologic Research
L Hunt, E M Hensor, J Nam, A N Burska, R Parmar, P Emery, F Ponchel
OBJECTIVES: Anticitrullinated protein antibody (ACPA)+ individuals with non-specific musculoskeletal symptoms are at risk of inflammatory arthritis (IA). This study aims to demonstrate the predictive value of T cell subset quantification for progression towards IA and compare it with previously identified clinical predictors of progression. METHODS: 103 ACPA+ individuals without clinical synovitis were observed 3-monthly for 12 months and then as clinically indicated...
October 2016: Annals of the Rheumatic Diseases
Linda Johansson, Natalia Sherina, Nastya Kharlamova, Barbara Potempa, Barbro Larsson, Lena Israelsson, Jan Potempa, Solbritt Rantapää-Dahlqvist, Karin Lundberg
BACKGROUND: The periodontal pathogen Porphyromonas gingivalis is hypothesized to be important in rheumatoid arthritis (RA) aetiology by inducing production of anti-citrullinated protein antibodies (ACPA). We have shown that ACPA precede RA onset by years, and that anti-P. gingivalis antibody levels are elevated in RA patients. The aim of this study was to investigate whether anti-P. gingivalis antibodies pre-date symptom onset and ACPA production. METHODS: A case-control study (251 cases, 198 controls) was performed within the Biobank of Northern Sweden...
2016: Arthritis Research & Therapy
Jayanth Doss, Huan Mo, Robert J Carroll, Leslie J Crofford, Joshua C Denny
OBJECTIVE: The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA. METHODS: A validated algorithm identified RA subjects from the de-identified EHR. Serotypes were determined by values of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA)...
September 2, 2016: Arthritis & Rheumatology
Rui-Xue Leng, Juan Liu, Xiao-Ke Yang, Bin Wang, Chao Zhang, Sha-Sha Tao, De-Guang Wang, Xiao-Mei Li, Xiang-Pei Li, Hai-Feng Pan, Dong-Qing Ye
OBJECTIVE: A recent genome-wide association study identified that genetic variants in DPP4 and CCR6 are connected with a risk of RA in the Han Chinese population. The aim of this study was to estimate the epistatic interaction between DPP4 and CCR6 in RA. METHODS: Two single-nucleotide polymorphisms identified in a Han Chinese genome-wide association study (rs12617656 in DPP4, rs1854853 in CCR6) were genotyped. Logistic regression was used to estimate the multiplicative interaction and the additive interaction was analysed by 2 × 2 factorial design...
September 1, 2016: Rheumatology
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